Biochemical and Radiological Changes in Liver Steatosis Following Mifepristone Treatment in Patients With Hypercortisolism

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder in Western industrialized countries and may progress to liver injury. Cortisol is thought to play a role in the pathogenesis of NAFLD, and cortisol modulation has shown efficacy in preclinical models. However, published reports on the clinical effects of glucocorticoid receptor antagonism in these patients are limited. CASE REPORT: Two women (aged 66 and 60 years) with endogenous hypercortisolism presented with a history of hepatic steatosis, hypertension, type 2 diabetes mellitus, and dyslipidemia. Both patients declined adrenalectomy or pituitary tumor surgery, and treatment with mifepristone 300 mg daily was initiated. During mifepristone treatment (follow up durations ranging from 10 months to 5 years), improvements in hypercortisolism-related cardiometabolic abnormalities were observed, including the normalization of lipid levels and improvement of hyperglycemia. In both cases, findings on follow-up imaging revealed resolution of fatty liver, which was supported by a decrease in liver enzymes on liver function tests. No adverse events were reported. DISCUSSION: NAFLD is frequently observed in patients with endogenous hypercortisolism. Improvement in liver function tests has previously been demonstrated in patients with hypercortisolism treated with mifepristone. The present cases showed, for the first time, radiological improvement of liver steatosis following mifepristone use in patients with hypercortisolism and NAFLD. CONCLUSION: This case series demonstrated improvements in biochemical and imaging parameters of NAFLD in patients with hypercortisolism treated with mifepristone. Further research is needed to investigate the effects of glucocorticoid receptor modulation in fatty liver disease.